Method of preparing esters of aryloxyphenoxy propanoic acid

ABSTRACT

An improved method of preparing aryloxyphenoxy propanoic acid esters is disclosed. Low-water levels and low temperatures increase the yield and decrease by-product formation. A hindered non-nucleophilic phenol, which is converted in situ to the phenate form, is added to the reaction mixture to drive the reaction to 99+% conversion.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of Ser. No. 494,196 filed May13, 1983, now abandoned.

BACKGROUND OF THE INVENTION

The present invention is directed to an improved method of preparingesters of aryloxyphenoxy propanoic acids. In particular, the presentinvention is directed to an improved method of preparing esters ofpyridyloxyphenoxy propanoic acids. The aryloxyphenoxy propanoic acidesters produced by the present invention are useful are herbicides.

Aryloxyphenoxy propanoic acid esters are generally prepared by a threestep process involving the neutralization of hydroquinone followed bycoupling with an aryl halide and then reacting the resultingaryloxyphenate with an appropriate halopropionate in an inert solvent atan elevated temperature in the presence of an alkaline material. Anexcess molar quantity of the halopropionate is usually employed becauseof competing side reactions. Because an excess of halopropionate isdesired, an almost instantaneous addition of halopropionate to thearyloxyphenate is required. This is impractical upon scale-up tocommercial production so the aryloxyphenate must be added to thehalopropionate. Since the aryloxyphenate must invariably be preparedfrom the reaction of an aryl halide with hydroquinone due to the lack ofcommercial availability of aryloxyphenates in large quantities, a secondreaction vessel is required so that the aryloxyphenate may be added tothe halopropionate.

U.S. Pat. No. 4,046,553 teaches a method of preparingα-[4-(5-mono-substituted or3,5-di-substituted-pyridyl-2-oxy)phenoxy]alkanecarboxylic acid esters byreacting a pyridyloxyphenol with a haloalkanecarboxylate in the presenceof an alkaline material at a temperature of about 40° C.-120° C. SeeColumn 11, lines 24-47; Column 12, lines 35-57; and Preparation Examples1 and 4.

British Patent Specification 1,599,121 teaches a method of preparingα-[4-(5-trifluoromethyl-2-pyridyloxy)phenoxy]alkane carboxylic acidesters by reacting a substituted pyridyloxyphenol with ahaloalkanecarboxylate in the presence of an alkaline material at atemperature of 40° C.-200° C. See Page 7, line 30 to Page 8, line 6;Page 8, lines 25 to 36; and Preparation Examples 1 and 3.

U.S. Pat. Nos. 4,214,086 and 4,275,212 teach methods of preparingaryloxyphenols by reacting aryl halides with hydroquinone in thepresence of a base such as NaOH or KOH. These reactions result in theformation of water.

U.S. Pat. No. 4,325,729 teaches a method of preparing pyridyloxyphenoxypropionates by reacting a pyridyloxyphenol with an α-halogencarboxylicacid derivative in the presence of a base. Reaction temperatures areindicated between 0° C.-200° C.

The present methods known to prepare aryloxyphenoxy propanoic acidesters by reacting an aryloxyphenate with a halopropionate, includingthose described above, suffer from disadvantages, such as, sidereactions resulting in the formation of undesirable by-products and arather low conversion (75-80%) of the starting materials to the desiredproducts. A base, such as, sodium or potassium carbonate, is usuallyadded to the reactants to increase the conversion to 99+% but introducesa solid waste problem. Because of the occurrence of side reactions, anexcess of halopropionate is normally employed which introducespurification steps and additional process steps for the recovery of theexcess halopropionate.

The present invention remedies the above problems encountered in thepreparation of esters of aryloxyphenoxy propionic acid. It has beendiscovered that water is a major cause of side reactions and isresponsible for the low conversion of the starting materials. It hasalso been discovered that elevated temperatures enhance the formation ofa bis(aryloxy)benzene by-product. The formation of this bis by-productis reduced when the third step of the reaction sequence is carried outat a temperature below about 35° C. The combination of a low water levelreaction and a low temperature reaction results in advantages, such as:the elimination of the need for additional base; a higher yield based onthe propionate starting material; a one vessel reaction; the eliminationof the step to recover excess propionate since near stoichiometricamounts of the propionate are employed; and a reduction in the sidereactions (by-products) caused by high temperature and high waterlevels.

SUMMARY OF THE INVENTION

The present invention provides a one-pot method of preparingaryloxyphenoxy propionic acid esters. The improvements are (a)conducting the third step of the reaction sequence in the presence ofless than about 1,000 parts per million by weight (ppm) water and (b)also conducting the third step of the reaction at a temperature belowabout 35° C. Each improvement, separately, is responsible for lessby-product formation thereby resulting in an improved yield of thedesired aryloxyphenoxy propionic acid ester. The improvements may bepracticed separately but are preferably combined and practiced togetherin a single operation.

Of particular interest in the practice of the present invention is animproved method of preparing an ester of2-(4-(((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoicacid, commonly known as haloxyfop;2-(4-(((3-fluoro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoicacid; or 2-(4-(((5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propionicacid, commonly known as fluazifop. Esters of particular interest includethe methyl, n-butyl, methoxypropyl and ethoxyethyl esters.

DETAILED DESCRIPTION OF THE INVENTION

More particularly, the present invention provides a method of preparingan ester of an aryloxyphenoxy propanoic acid of the formula ##STR1##wherein Ar represents an aryl group; and

R represents C₁ -C₈ alkyl or C₃ -C₆ alkoxyalkyl;

which comprises forming ##STR2## wherein Ar is as defined above;

by the reaction of ArX with the dianion of hydroquinone, reducing thewater content of the reaction mixture to less than 1,000 ppm andthereafter, without isolation of the phenate intermediate, reacting withan excess stoichiometric amount of a propionate of the formula ##STR3##wherein R is as defined above; and

B represents Cl or Br.

An additional improvement in the present reaction is achieved when thereaction is conducted at a temperature below about 35° C. Preferably,both the low water (<1,000 ppm) and low temperature (<35° C.) reactionconditions are carried out together in the same reaction resulting in animproved yield of the desired product.

LOW-WATER CONDITION

The low-water reaction condition can be achieved by distilling off waterpresent in the aryloxyphenate/inert medium mixture before the propionatereactant is added. The water is distilled off until the water level inthe reaction mixture is less than about 1,000 ppm, advantageously lessthan about 500 ppm, preferably less than about 250 ppm and mostpreferably less than about 125 ppm.

Water can be introduced into the reaction mixture in a number of ways.The most common way water is introduced into the reaction mixture isfrom the preparation of the aryloxy phenate. The reaction ofhydroquinone with a base, such as, NaOH, KOH or NH₄ OH, in an inertcarrier, forms a hydroquinone dianion and water. This hydroquinonedianion is reacted with an arylhalide to form the aryloxyphenatestarting material. Attempts to distill the water out of the hydroquinonedianion/carrier reaction mixture after formation of the hydroquinonedianion but before the reaction with the arylhalide fail to get thewater level below about 2,000 ppm. It has been surprisingly found thatthe addition of an effective amount of methanol to the hydroquinonedianion/carrier/water reaction mixture will promote the distillation ofthe water from the reaction mixture. The methanol will distill first,followed by the water, second. Usually methanol is added to the reactionmixture in an amount by weight that is at least about equivalent to theamount of water by weight that will be in the reaction mixture afterformation of the hydroquinone dianion. Preferably, the weight ratio ofmethanol:water in the reaction mixture will be about 2:1.

It has also been surprisingly found that distillation after thehydroquinone dianion is reacted with the aryl halide to form thearyloxyphenate removes water from the reaction mixture to levels about1,000 ppm or less. If the distillation is carried out long enough, waterlevels of about 125 ppm or less are achievable.

Alternatively, low water levels are achieved by preparing thehydroquinone dianion by reacting hydroquinone with an alkali metalalkoxide, such as, for example NaOCH₃, KOCH₃, NaOCH₂ (CH₂)₂ CH₃, KOCH₂(CH₂)₂ CH₃, KOC₂ H₅ or NaOC₂ H₅, in an inert medium such as, for exampledimethylsulfoxide (DMSO), whereby the hydroquinone dianion and thecorresponding alcohol are formed. This procedure avoids the formation ofwater in the preparation of the hydroquinone dianion. The resultingalcohol is readily distilled off from the reaction mixture.

The metal alkoxides employed in preparing the hydroquinone dianion arewell known compounds and can be prepared employing well knowntechniques. Suitable metal alkoxides include, for example, alkali metalalkoxides, such as, NaOCH₃, NaOCH₂ (CH₂)₂ CH₃ and NaOC₂ H₅. NaOCH₃ andHaOC₂ H₅ are prepared by reacting sodium metal with anhydrous methanol,n-butanol or ethanol to make a solution of the corresponding alkoxide inthe corresponding alcohol. The metal alkoxide solution is reacted withhydroquinone under N₂ in an inert medium (DMSO) to make the hydroquinonedianion. The alcohol is then distilled off and the hydroquinone dianionis reacted with an aryl halide to form the aryloxyphenate startingmaterial whereby substantially no water is present in the reactionmixture.

LOW-TEMPERATURE CONDITION

Because the present reaction is exothermic, the low temperature reactioncondition can be achieved by (1) adding the propionate starting materialslowly to the aryloxyphenate so that the temperature of the reactionmixture does not exceed about 35° C. or (2) cooling the reaction mixturewith an external cooling means so that the reaction mixtures does notexceed about 35° C. Advantageously, the reaction mixture is maintainedthroughout the reaction at a temperature below about 30° C. andpreferably at or below about 25° C.

Suitable for use as an inert carrier medium are polar aprotic solvents,such as, DMSO, dimethylformamide (DMF), dimethylacetamide,diethylacetamide, sulpholane and N-methylpyrrolidinone. A preferredinert carrier medium is DMSO.

The present improvements provide a reaction wherein less by-productformation is observed but provides about a 95% conversion of thearyloxyphenate starting material. To drive the reaction to completion aneffective amount of a hindered non-nucleophilic phenol, which isconverted in situ to the phenate form, is added to the reaction. Aneffective amount of a hindered phenol will drive the reaction to 99+%conversion. A preferred hindered phenol is 2,6-di-t-butyl-4-methylphenol (BHT). Usually at least about 0.05 mol of hinderednon-nucleophilic phenol per mole of aryloxyphenate is added to thepresent reaction, i.e., about 5 mol percent.

When a metal or ammonium hydroxide or an alkoxide is reacted withhydroquinone to form the hydroquinone dianion, a slight excess hydroxideor alkoxide is advantageously employed. This slight excess of hydroxideor alkoxide converts the hindered non-nucleophilic phenol in situ to thephenate form. A hindered non-nucleophilic phenol can be added to thehydroxide or alkoxide and hydroquinone reactants in an amount that isabout equivalent to the slight excess of hydroxide or alkoxide. Forexample, if 2.05 mols of NaOH are reacted with 1.0 mol of hydroquinone,then about 0.05 mol of hindered non-nucleophilic phenol is added to thereactants which is thereafter reacted with the aryl halide to form thearyloxyphenate. Upon addition of the propionate, and without isolationof the phenates, a 99+% conversion of starting materials is achieved.

Suitable aryloxyphenate reactants for the second step of the reactionsequence include quinolinyloxyphenates, phenyloxyphenates,pyridyloxyphenates, quinoxalinyloxyphenates, benzoxazoloxy phenates andbenzothiazolyloxyphenates. Preferred reactants for the second step ofthe reaction sequence include 4-(pyridyl-2-oxy)phenates of the formula##STR4## wherein X and Y each independently represents CF₃, H, Cl, F, Bror I. The aryloxyphenates described above are known compounds and can beprepared employing techniques well-known in the art, such as, forexample by the reaction of an arylhalide with the dianion ofhydroquinone.

Suitable propionate reactants include compounds of the formula ##STR5##wherein B represents Cl or Br; and

R represents C₁ -C₈ alkyl or C₃ -C₆ alkoxyalkyl.

These propionate reactants are for the most part known compounds and canbe prepared employing techniques well-known in the art. Preferredpropionates are those compounds wherein R is n-butyl, methyl,methoxypropyl (C₃ H₆ OCH₃) or ethoxyethyl (C₂ H₄ OC₂ H₅). Methoxypropylpropionates are compounds of the formula ##STR6## wherein X represents--Cl or --Br;

R¹ represents --H or --CH₃ ; and

R² represents --H or --CH₃ ;

with a first proviso that when R¹ is --H, then R² is --CH₃ and a secondproviso that when R¹ is --CH₃ then R² is --H.

Such compounds are prepared by employing procedures analogous tostandard, well-known procedures used for preparing structurally relatedcompounds. For example, such compounds can be prepared by the acidcatalyzed esterification of a 2-substituted propionic acid.

Such compounds can also be prepared by the transesterification of themethyl ester of a 2-substituted propionic acid employing an alkyltitanate catalyst.

The reaction of the present invention can be characterized by thefollowing chemical equation: ##STR7## wherein Ar represents phenyl,pyridyl, quinolinyl, quinoxalinyl, benzoxazolyl or benzothiazolyl and Band R are as defined above. No attempt has been made to balance theabove equation. A hindered non-nucleophilic phenol, which is convertedinto the phenate form in situ, may be added to the reactants to drivethe reaction to 99+% conversion.

In one embodiment of the present invention,4-(5-(trifluoromethyl)pyridinyl-2-oxy)phenate is prepared and reacted insitu with an appropriate propionate, employing the low water and lowtemperature conditions described herein, resulting in the formation ofthe corresponding ester of2-(4-(((5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propionic acid. Thethird step of this reaction sequence can be characterized as follows:##STR8## wherein B and R are as hereinbefore defined.

In a preferred embodiment of the present invention,4-(3-chloro-5-(trifluoromethyl)pyridinyl-2-oxy)phenate is prepared andreacted in situ with an appropriate propionate, employing the low-waterand low temperature conditions described herein, resulting in theformation of the corresponding ester of2-(4-(((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propionicacid. The third step of this reaction sequence can be characterized asfollows: ##STR9## wherein B and R are as hereinbefore defined.

In another embodiment of the present invention,4-(3-fluoro-5-(trifluoromethyl)pyridinyl-2-oxy)phenate is prepared andreacted in situ with an appropriate propionate, employing the low-waterand low temperature conditions described herein, resulting in theformation of the corresponding ester of2-(4-(((3-fluoro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propionicacid.

Once prepared, the aryloxyphenoxy propionates formed by the presentreaction are recovered employing standard, well-known, extraction andpurification techniques, such as, for example, solvent extraction withmethylene chloride.

The following examples illustrate the practice of the present inventionbut should not be construed as limiting its scope. No attempt has beenmade to balance any chemical equations described herein. Water leveldeterminations were made by the KARL-FISHER method.

EXAMPLE 1

A 250 milliliter (ml), 3-neck, round bottom flask, equipped with athermowell, addition funnel, air-driven stirrer and a 20 centimeter(cm)×1 cm vigreaux column with distillation head, was purged with N₂ andloaded with 100 ml of DMSO and 11 grams (g) (0.1 mol) of hydroquinone.The addition funnel was loaded with 16 g of 50% NaOH (0.2 mol). Theflask was heated to approximately 60° C. where the system was degassedby pulling a vacuum until the DMSO started boiling and then releasingthe vacuum with N₂. The system was degassed three (3) times in thismanner and the vacuum was set at approximately 100 millimeters (mm). Thetemperature was increased to approximately 95° C. and the NaOH was addedover a 5-10 minute period causing the dianion of hydroquinone toprecipitate. The temperature was increased to distill off the water at apot temperature of approximately 105°-125° C. and a head temperature of50°-124° C. When only DMSO was coming overhead (about 25 g ofdistillate), the temperature was decreased to approximately 80° C. andthe vacuum was released to N₂. Keeping the temperature of the reactionmixture below 90° C., 21.6 g (0.1 mol) of2,3-dichloro-5-(trifluoromethyl)pyridine was added over a 10-20 minuteperiod. The reaction mixture was kept at a temperature between 80°-90°C. for 1-11/2 hours whereby4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)phenate was formed. At thispoint the reaction mixture contained from 2,000-5,000 ppm water. About30-50 g of DMSO was distilled off from the reaction mixture at 80° C./15mm which reduced the water level from 5,000 ppm to less than about 120ppm. The reaction mixture was cooled to 25° C. and 13.5 g (0.11 mol) ofmethyl 2-chloropropionate was added over a 15 minute period so that thetemperature remained under 30° C. After 5 hours at room temperature, theconversion of 4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)pheneate to2-(4-((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propionicacid, methyl ester was 96%. The product mixture was filtered. Theprecipitate was washed with four (4) 25 ml portions of methylenechloride. The combined filtrates were extracted with one (1) 50 ml andthree (3) 20 ml portions of water. The water was made acidic with HCl tobreak emulsions. The organic phase was solvent stripped on a rotavap at70° C./20 mm for 30 minutes to give 37 g of crude product assaying atapproximately 91%2-(4-((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy propionicacid, methyl ester. The unoptimized yield based on propionate was 81.5percent.

EXAMPLE 2

Sodium metal was added to methanol to make a 20% by weight solution ofNaOCH₃ in methanol. 54 g (0.2 mol NaOCH₃) of the NaOCH₃ in methanolsolution was placed in an N₂ purged flask with 0.1 mol hydroquinone and100 ml DMSO. Most of the alcohol was stripped out at atmosphericpressure until the pot temperature reached approximately 130° C. The potwas cooled to approximately 60° C. and put under a 100 mm vacuum. Theremaining alcohol was taken overhead until only DMSO was comingoverhead. 21.6 g (0.1 mol) of 2,3-dichloro-5-(trifluoromethyl)pyridinewas added to the reaction mixture resulting in the formation of4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)phenate. At this point thewater content of the reaction mixture was 100-250 ppm H₂ O.Substantially the same procedures described in Example 1 were repeatedresulting in the formation of2-(4-((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy propionicacid, methyl ester in a good yield.

EXAMPLE 3

A mixture of DMSO (1089 g), hydroquinone (88.0 g; 0.80 mol) and IONOL®brand 2,6-di-tert-butyl-4-methylphenol (8.8 g; 0.04 mol) was distilledat ˜35 mm for 1.5 hours (Pot=105° C.; Head=99° C.). 249 g of distillatewas collected. The temperature of the mixture was reduced to 85° C. and336.5 g (1.63 mols) of sodium methoxide in methanol (26.2% by weight)was added to the mixture rapidly. The mixture was then heated under N₂for one (1) hour resulting in 229.4 g of methanol distillate(Pot=103°-138° C.; Head=66° C.). The mixture was cooled to 85° C. Undera vacuum of 100 millimeters (mm) the mixture was further distilled foran additional hour resulting in 136.3 g of methanol distillate (Pot=125° C.; Head=124° C.). The temperature of the mixture was lowered to80° C. and 2,3-dichloro-5-(trifluoromethyl)pyridine (169.0 g; 0.7566mol) of 97% purity was added to the mixture over a 20 minute period. Themixture was continuously mixed for two (2) hours resulting in theformation of 4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)phenate. Atthis point the water level in the reaction mixture was determined to be381 ppm. The temperature of the reaction mixture was reduced to 25° C.and methyl 2-chloropropionate (100.7 g; 0.822 mol) was added to thereaction mixture over a 35 minute period whereby the temperature of thereaction mixture fluctuated between 20° C. and 28° C. After 45 minutesof continuous stirring, analysis of the reaction mixture indicated a99+% conversion of the4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)phenate. The reactionmixture (1116 g) was continuously stirred overnight. In the morning, thereaction mixture was diluted and mixed with 700 ml of perchloroethylene,350 ml of H₂ O and 15 ml of concentrated HCl resulting in the formationof 3 layers: a top organic layer, a middle emulsion layer and a bottomaqueous layer. The organic layer was separated and the aqueous andemulsion layers were diluted and mixed with 200 ml of perchloroethylene,100 ml of H₂ O and 5 ml of concentrated HCl resulting in the formationof 3 layers again. The organic layers were combined and extracted withtwo (2) 500 ml portions of H₂ O. The solvent was stripped at 90° C./20mm for 1.5 hours to give 343.3 g of product containing 77.2% by weightof 2-(4-(((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy propionicacid, methyl ester. This represents a yield of 92.9% of theoreticalbased on the 2,3-dichloro-5-(trifluoromethyl)pyridine starting materialand an optimized yield of 85.9% of theoretical based on the methyl2-chloropropionate starting material.

EXAMPLE 4

Substantially the same procedures described in Example 3 were repeatedexcept that ethoxy ethyl 2-chloropropionate was employed instead ofmethyl 2-chloropropionate. The resulting product, i.e.,2-(4-((3-chloro-5-trifluoromethyl)-2-pyridinyl)oxy)phenoxy propionicacid, ethoxy ethyl ester, was formed in a good yield (92% based onpyridine starting material). The unoptimized yield based on propionatewas 81 percent.

EXAMPLE 5

A mixture of DMSO (360 ml), hydroquinone (55.0 g; 0.5 mol), IONOL® brandBHT (5.7 g; 0.026 mol) and anhydrous methanol (135 ml) was degassed atroom temperature and left under an N₂ atmosphere. Aqueous NaOH (82.7 g;1.025 mols) (49.5% by weight) was added to the mixture and the mixturewas distilled for one (1) hour and 10 minutes (Pot=110° C.-130° C.;Head=64°-72° C.). 95 ml of distillate was collected which contained 9%by weight water. A total of 120 ml of DMSO was continuously fed into themixture during the distillation. The temperature of the reaction mixturewas decreased to <80° C. Under a vacuum of 95 mm the mixture was furtherdistilled for 4 hours (Pot=80° C.-125° C.; Head=32°-123° C.) resultingin 310 g of distillate. The mixture was cooled and2,3-dichloro-5-(trifluoromethyl)pyridine (102.5 g; 0.46075 mol) of 97%purity was added to the reaction mixture. The mixture was kept at 95°C., with continuous stirring for 4 hours and 10 minutes. At this point,the reaction mixture contained 497 ppm water. The mixture was cooled toabout 25° C. and methyl 2-chloropropionate (66.1 g; 0.54 mol) was addedover a 5 minute period whereby the temperature of the mixture was keptunder 27° C. The mixture was stirred at room temperature overnight. Thedesired product was then recovered by solvent extraction, employingmethylene chloride and acidified water, in a yield of 90.5% oftheoretical based on the 2,3-dichloro-5-(trifluoromethyl)pyridinestarting material. The unoptimized yield based on propionate was 77percent.

EXAMPLE 6

Sodium hydroxide pellets (10.94 g; 0.26 mol) containing about 95% NaOHand 65 ml of anhydrous methanol were mixed and stirred overnight underN₂. In the morning, hydroquinone (14.0 g; 0.127 mol), IONOL® brand BHT(1.50 g; 0.0068 mol) and 130 ml of DMSO were mixed and added rapidly tothe NaOH/methanol mixture. The reaction mixture was kept under N₂,heated and distilled for 2.25 hours (Pot=130° C.; Head=60°-64° C.). Themixture was cooled to <80° C. and put under a vacuum of 105 mm. Themixture was reheated. Distillation occurred for 1.5 hours, stopped forabout 2 hours, then occurred again for 45 minutes (Pot=80°-123° C.;Head=55°-112° C.). The distillate in the last 45 minutes weighed about30 g and was mostly DMSO. 2,3-Dichloro-5-trifluoromethyl)pyridine (26.7g; 0.12028 mol) of 97% purity was added to the reaction mixture over a 5minute period. The reaction mixture was stirred continuously at 85°-90°C. for one (1) hour and 35 minutes. Analysis of the reaction mixtureindicated there was about 495 ppm H₂ O. The reaction mixture was cooledto 25° C. and methyl 2-chloropropionate (17.2 g; 0.14 mol) was added.The reaction mixture was left at room temperature overnight withcontinuous stirring. Analysis indicated a 99+% conversion of4-(3-chloro-5-(trifluoromethyl)pyridyl-2-oxy)phenate. The unoptimizedyield based on propionate was 71.4 percent.

EXAMPLE 7

IONOL® brand BHT (1.11 g; 0.005 mol) and hydroquinone (11.0 g; 0.10 mol)were dissolved in 100 ml of DMSO in a N₂ purged flask. Sodium methoxide(42.25 g of a 26.2% CH₃ O.sup.⊖ /CH₃ OH solution; 0.205 mol) was addedto the reaction mixture. The reaction mixture was distilled for 1 hourand 10 minutes under a 100 mm vacuum (Pot=55°-124° C.; head=23°-124°C.). The reaction mixture was cooled to 58° C. and2-chloro-5-(trifluoromethyl)pyridine (18.2 g; 0.10 mol), dissolved in 10ml of DMSO, was added thereto. The reaction mixture was heated tobetween 80°-90° C. for 2 hours. At this point, the reaction mixturecontained 120 ppm H₂ O. The reaction mixture was cooled to 20° C. andn-butyl 2-chloro-propionate (18.1 g containing 220 ppm H₂ O; 0.11 mol)was added to the reaction mixture while the temperature of the reactionmixture was maintained at room temperature with continuous stirring for2.5 hours. Analysis indicated a 99+% conversion and a yield of about 95%based on pyridine. The yield based on propionate was 86 percent.

Various other aryloxyphenoxy propionic acid esters, described herein,are made in a good yield when low water levels and low temperatures, asdescribed herein, are employed in the reaction of the appropriatearyloxyphenol with the appropriate propionate.

I claim:
 1. In a method of preparing an ester of an aryloxyphenoxypropanoic acid of the formula ##STR10## wherein X represents H, CF₃, Cl,F, Br or I;Y represents Cl, H, F, Br, CF₃ or I and R represents C₁ -C₈alkyl or C₃ -C₆ alkoxyalkyl;which comprises forming ##STR11## by thereaction of ##STR12## wherein X and Y are as defined above and hal isCl, F, Br, or I, with the dianion of hydroquinone under an inertatmosphere while maintaining the water content of the reaction mixtureat less than 1,000 ppm and thereafter, without isolation of the phenateintermediate, reacting with an excess stoichiometric amount of apropionate of the formula ##STR13## wherein R is as defined above; and Brepresents Cl or Brat a temperature that does not exceed 35° C. 2.Method of claim 1 wherein the dianion of hydroquinone is formed by thereaction of hydroquinone with an alkali metal alkoxide.
 3. Method ofclaim 2 wherein the alkali metal alkoxide is sodium methoxide.
 4. Methodof claim 1 wherein the dianion of hydroquinone is formed in an inertcarrier/water reaction mixture and methanol is added to facilitate theremoval of water by distillation.
 5. The method of claim 1 wherein X isCF₃ and B is Cl or Br.
 6. The method of claim 5 wherein Y is H or Cl. 7.The method of claim 6 wherein R is CH₃, n-butyl, C₃ H₆ OCH₃ or C₂ H₄ OC₂H₅.
 8. The method of claim 7 wherein the water content is about 500 ppmor less.
 9. The method of claim 8 wherein the water content is about 250ppm or less.
 10. The method of claim 9 wherein the water content isabout 125 ppm or less.
 11. The method of claim 8 wherein Y is Cl. 12.The method of claim 11 wherein R is CH₃ or C₂ H₄ OC₂ H₅.
 13. The methodof claim 8 wherein Y is H.
 14. The method of claim 13 wherein R isn-butyl.
 15. The method of claim 1 comprising a third improvement ofadding to the reactants an amount of a hindered non-nucleophilic phenol,which converts in situ to the phenate form, effective to drive thereaction to greater than 99 percent conversion.
 16. The method of claim15 wherein the hindered non-nucleophilic phenol is2,6-di-tertiary-butyl-4-methyl phenol.